The main objective of the proposed research is to synthesize a number of liponucleotides for evaluation of antitumor activity. The design of the liponucleotides is based in part on the structure, chemistry, and biologic function of cytidine diphosphate diglycerides (CDP-diglycerides) in phosphoglyceride metabolism and cell membrane biogenesis, and in part on the established clinical use of antimetabolic nucleosides and nucleotides. The novel structures and physicochemical properties of liponucleotide analogs would provide the opportunity to investigate the possibility of controlling or enhancing selective transport of drug molecules to tumor sites and to interfere with cell membrane biogenesis through inhibition of phosphoglyceride biosynthesis. A significant application of the proposed research would be in the area of central nervous system (CNS) cancer chemotherapy. Chemical syntheses would be carried out using methods of phospholipid and nucleoside chemistry, and antitumor evaluation would include cell culture, toxicological, and animal tumor studies.